p53 over-expression identifies a subset of nodal peripheral T-cell lymphomas with a distinctive biological profile and poor clinical outcome

Peripheral T-cell lymphomas (PTCL) are usually characterized by aggressive clinical behaviour and poor clinical outcome, but their biological backgrou nd has not been extensively investigated to date, due to their low incidenc e, about 10%, of all non-Hodgkin's lymphoma cases in Western countries, and also to the paucity of specific molecular-genetic abnormalities. Neverthle ss, there is increasing biological and clinical evidence that primary nodal PTCL should be considered separately from extra-nodal cases, but little is known about biological factors of possible clinical and prognostic impact. This immunohistochemical study has analysed the expression of p53, Mdm2, p 21(WAF1), BCL-2 and p-glycoprotein (MDR-1 gene product) in a series of 45 c ases of nodal peripheral T-cell lymphomas (PTCL) with 'high-grade' histolog y. The immunohistochemical findings were then correlated with proliferative activity and clinical outcome. p53 was overexpressed in 13 cases (28.9%). p53 positive cases showed significantly higher proliferative activity (p <0 .01), more frequent expression of Bcl-2 (p <0.01) and less frequent express ion of p21(WAF1) than p53 negative cases. Mdm2 and p-glycoprotein were expr essed in 4/13 (30.8%,) and 8/13 (61.5%.) p53 positive cases respectively, a nd in none (0%.) of the p53 negative cases (p <0.01). Analysis of the survi val curves showed that p53 positive cases were associated with a significan tly poorer clinical outcome than p53 negative cases, in terms of both overa ll survival (p = 0.0032) and event-free survival (p = 0.0004). Furthermore, multivariate analysis showed that p53 expression was the most important in dependent prognostic variable. These findings indicate that p53 overexpress ion identifies a subset of nodal PTCL cases with a distinctive biological p rofile (higher proliferative activity, less frequent expression of p21(WAF1 ) and more frequent expression of Bcl-2, Mdm2 and p-glycoprotein than p53 n egative cases) and poor clinical outcome. The immunohistochemical analysis of p53 expression is a simple, rapid and low-cost method which may provide information of potential clinical and prognostic value in nodal peripheral T-cell lymphomas. Copyright (C) 2001 John Wiley & Sons, Ltd.